PXD007851

PXD007851 is an original dataset announced via ProteomeXchange.

Title	A Chemproteomics Approach to Query the Degradable Kinome Using a Multi-kinase Degrader
Description	Heterobifunctional molecule that recruits E3 ubiquitin ligases, such as cereblon, for targeted protein degradation is an emerging pharmacological strategy. A major unanswered question is how generally applicable this strategy is to all protein targets. In this study, we designed a multi-kinase degrader by conjugating a highly promiscuous kinase inhibitor with a cereblon-binding ligand, and used quantitative proteomics to discover 28 kinases, including BTK, PTK2, PTK2B, FLT3, AURKA, AURKB, TEC, ULK1, ITK and 9 members of the CDK family, as degradable. This set of kinases is only a fraction of the intracellular targets bound by the degrader, demonstrating that successful degradation requires more than target engagement. The results guided us to develop selective degraders for FLT3 and BTK, with potentials to improve disease treatment. Together, this study demonstrates an efficient approach to triage a gene family of interest to identify readily degradable targets for further studies and pre-clinical developments.
HostingRepository	PRIDE
AnnounceDate	2017-11-08
AnnouncementXML	Submission_2018-05-23_06:17:32.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Eric Fischer
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-27 02:35:42	ID requested
1	2017-11-08 00:04:17	announced
⏵ 2	2018-05-23 06:17:34	announced	Updated publication reference for PubMed record(s): 29129717.

Huang HT, Dobrovolsky D, Paulk J, Yang G, Weisberg EL, Doctor ZM, Buckley DL, Cho JH, Ko E, Jang J, Shi K, Choi HG, Griffin JD, Li Y, Treon SP, Fischer ES, Bradner JE, Tan L, Gray NS, A Chemoproteomic Approach to Query the Degradable Kinome Using a Multi-kinase Degrader. Cell Chem Biol, 25(1):88-99.e6(2018) [pubmed]

curator keyword: Biological

submitter keyword: kinase

Eric S. Fischer
contact affiliation	BCMP, Harvard Medical School, Boston, USA Cancer Biology, Dana-Farber Cancer Institute, Boston, USA
contact email	eric_fischer@dfci.harvard.edu
lab head
Eric Fischer
contact affiliation	Dana-Farber Cancer Institute
contact email	eric_fischer@dfci.harvard.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2017/11/PXD007851

PRIDE project URI

• PRIDE
  1. PXD007851
     1. Label: PRIDE project
     2. Name: A Chemproteomics Approach to Query the Degradable Kinome Using a Multi-kinase Degrader